The way the liver renews itself may be simpler than what scientists had been assuming

[Guest guest]

The way

the liver renews itself may be simpler than what scientists had been assuming. A new study, appearing in the April 13 issue of The

Journal of Biological Chemistry, provides new information on the inner workings

of cells from regenerating livers that could significantly affect the way

physicians make livers regrow in patients with liver

diseases such as cirrhosis, hepatitis, or cancer.

" The

human liver is one of the few organs in the body that can regenerate from as

little as 25 percent of its tissue, " says Seth Karp, assistant professor

of surgery at Harvard Medical

School, Boston,

and main author of the study. " It is not known

how the liver does it, but our results provide some details of what makes the

liver so unique. "

Although

organ regeneration has been observed in many animals, the details of how it

happens at the cellular level are still not completely understood. So far, scientists have shown that cells that participate

in tissue regeneration behave as if they were part of a growing organ in an

embryo. In other words, the cells act as if the liver

is growing, as do other organs in a developing embryo.

Many of

the proteins that induce organ regeneration have been identified and scientists

are now trying to make organs regrow by stimulating

these proteins. Regrowing

livers this way would be especially useful for patients whose livers are so

damaged – say, by a tumor that has spread to most of the liver –

that a large part would be removed. Unless such

patients receive the right amount of liver transplant from an organ donor, they

do not always survive. Quickly stimulating the growth

of the remaining portion of their liver could be their only chance of survival.

To

investigate how the liver regenerates, Karp and his colleagues set out to

determine which proteins are involved in the regenerating cells. The scientists were also interested in testing whether

regenerating cells behave like embryonic ones, as is commonly assumed for other

organs. New processes may explain why the liver is so

uniquely capable of renewal and repair after injury, the scientists thought.

Karp's

team considered two samples of mice. The first

consisted of embryonic mice at various stages of development while the second

was composed of adult mice to which two-thirds of their liver were removed. Using techniques such as DNA microarrays

– which determine which genes are active in a cells – and software programs that analyze the collected information, the

scientists listed all the proteins that help the cells grow and proliferate in

both samples.

The

results were unexpected. The researchers noticed that

only a few proteins were common to both processes. Proteins

called transcription factors, which affect DNA in the cell's nucleus, were

highly involved in the development of embryos' livers but not in adult liver

regeneration. Instead, proteins that help cells

proliferate were active in both the developing and regenerating livers.

These

findings showed that a regenerating liver does not behave as a developing

embryo. Instead, regeneration could actually be only

due to an increase in cells that multiply through regular cell divisions, a

process called hyperplasia.

The new

results may also have important medical implications. Transcription

factors are known to be more difficult to manipulate than the other identified

proteins. Since the transcription factors were not

present in regenerating livers, it might be easier to stimulate liver

regeneration by only activating the other identified proteins.

" These

results are very encouraging, " Karp says. " Not

only did we discover that the number of proteins involved in liver regeneration

is relatively low, but they don't include transcription factors, so we may be

closer to being able to stimulate liver regeneration than we thought. "

The next

step will be for scientists to understand whether the regenerating cells are

stem cells. Studies have shown that adult stem cells

are involved in the repair of many organs, but in the case of the liver, the

cells repairing it through regeneration may simply be regular cells, not stem

cells.

" We

think that the liver regrows through a relatively

simple process, which could explain its prodigious ability to repair

itself, " Karp says. Source : American Society for

Biochemistry and Molecular Biology

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